The present invention relates to compositions based on amino acids for preventing and/or reducing tissue damage brought about by multiple metabolic dysfunctions which appear, especially as a result of a sepsis.
Infection may be independent of any other pathology, but infection most commonly occurs in man after a surgical operation or is associated with a trauma, a burn, diabetes, a cirrhosis, a neoplasm, or the like. Infection may also occur during treatment with immunosuppression, cytolytic or cytostatic agents. Septic illnesses are also strongly correlated with a state of malnutrition, very especially in young children and in elderly people. Such illnesses are also found in animals such as domestic animals and especially in industrial stockraising (pigs, chickens, and the like).
The metabolic response to infection is complex and, up to the present, very many issues still remain unexplained. This complexity results in particular from the participation of many factors: modification in the supplies of the substrates to the various organs and in their use, variation in the sensitivity and the reactivity of the tissues to the hormones, for example resistance to insulin, change in blood flow rates, participation of many mediators such as PAF, or cytokines (interleukins, TNF, and the like), the pharmacological effects of which may be in conflict according to the tissue under consideration.
The response to infection is dynamic, with several phases whose intensity and duration depend on the severity of the attack and on the time at which infection occurs with respect to the attack. Three periods are usually distinguished (Cuthbertson, 1942). The "ebb phase"--the 24 hours after the attack which is characterized by a rapid mobilization of the energetic substrates and a reduced metabolic activity. The ebb phase is followed by the "flow phase", the duration of which varies from a few days to 2 to 3 weeks. This period sees a metabolic activity increase with the result of a general catabolism of the tissues, in particular of the muscle. The last phase, in survivors, corresponds to the convalescence, which is anabolic.
The present invention is more particularly targeted at treating or preventing by nutritional compositions the dysfunctions which take place in the first two phases. These phases are characterized by the existence of an anorexia and a hypermetabolic response which is reflected clinically by the weight loss and especially a wasting away in muscle proteins, by an inflammatory state, the existence of a tachycardia, a hyperventilation, an increased oxygen consumption, a disfunction of the immune system, and the like.
Accelerated loss in proteins from the muscle is used to deal with:
--the increased requirements for glucose of the body by means of hepatic neoglucogenesis and for glutamine, an essential energy source for the cells of the intestinal mucous membrane or for the rapid multiplication cells of the immune system,
--the amino acid requirements for the increased protein syntheses of several organs, in particular of inflammatory proteins in the liver.
The actions of the hormones and of certain mediators, such as .alpha.-TNF, have been the subject and still form the subject of many evaluations. Although certain mechanisms are beginning to be better explained, with respect to the specific nutritional requirements and more particularly those which concern amino acids, very little is known in the case of sepsis or of post-attack inflammatory reactions.